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Which biologic drug most effectively treats generalized psoriasis? A recent study pitted two effective biologics, etanercept and ustekinumab, against each other in a randomized, single-blinded clinical trial in 903 patients. All patients had moderate to severe psoriasis, with at least 10% of the total body area affected.
Patients were randomly assigned, in a 3:5:5 ratio, to receive injections of ustekinumab 45 mg or ustekinumab 90 mg at weeks 0 and 4, or of etanercept 50 mg twice weekly for 12 weeks. The primary endpoint was a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) scores at week 12. This endpoint was achieved by 68% of 45-mg ustekinumab recipients and 74% of 90-mg ustekinumab recipients, versus 57% of the etanercept recipients (P=0.01 and P<0.001, respectively). The secondary endpoint was physician-evaluated global response. Physicians rated 65% of the 45-mg ustekinumab recipients and 71% of the 90-mg ustekinumab recipients as being clear or nearly clear of psoriasis, compared with 49% of the etanercept recipients (P<0.001 for both). The clinical response was also faster in the ustekinumab groups. Almost half (49%) of etanercept nonresponders achieved 75% improvement in PASI scores when they crossed over to ustekinumab after 12 weeks.
All reactions were mild. Rates of drop-out and adverse events were about the same in all three groups. No subjects developed anaphylactic reactions. Serious infections were rare.
Griffiths CEM et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med 2010 Jan 14; 362:118.
Comment
This trial was sponsored by the manufacturer of ustekinumab, and it was not double-blinded. Nevertheless, it is a large randomized study in which more patients with severe psoriasis responded to ustekinumab than to etanercept at standard dosing regimens. Injection site reactions occurred in 25% of patients receiving etanercept and in about 4% of patients receiving ustekinumab. Of course, the etanercept recipients had 24 injections, in contrast to only 2 for ustekinumab.
These results are predictable given the findings of earlier clinical trials that compared each agent against placebo. Psoriasis is a chronic disease that might require lifetime treatment. In selecting the appropriate therapy, we must balance effectiveness against toxicity. While ustekinumab is clearly more effective and requires fewer injections in the short term, we don't know whether its effectiveness will endure or if unexpected toxicity will become evident with widespread use outside the study environment.